Advances in Allergy/Immunology 2014 Nothing to declare Katherine - PDF document

10/14/2014 Advances in Allergy/Immunology 2014 Nothing to declare Katherine Gundling, MD, FACP Professor University of California, San Francisco Manifestations of “Allergy”! Order of Presentation Itching of the eyes, nose, Rhinitis throat Conjunctivitis Drainage Asthma Respiratory allergy update Headache Sinusitis Influenza Vaccination Cough or throat clearing Anti ‐ IgE for urticaria “Bronchitis” General misery Poor performance in school or at work Mesquite, by ZooFari 1

10/14/2014 Allergic Rhinitis/Asthma/Conjunctivitis Allergic Rhinitis/Asthma/Conjunctivitis Inhaled Allergens Inhaled Allergens Categories of Management options: Categories of Management options: 1. Maximal preventive measures 1. Maximal preventive measures 2. Treatment of symptoms 2. Treatment of symptoms 3. Retraining of the immune system 3. Retraining of the immune system 2. Treatment of Symptoms 2. Treatment of Symptoms Saline (rarely, budesonide) irrigation Leukotriene inhibitors Oral antihistamines (multiple) Receptor blockers (montelukast, zafirlukast) Production inhibitors (zileuton) Nasal sprays Inhaled agents Corticosteroids (multiple) Corticosteroids (multiple) Antihistamines (azelastine) Corticosteroid/LABA (multiple) Decongestants (oxymetazoline) Anticholinergics (ipratropium/tiotropium) Mast cell stabilizers (cromolyn sodium) Mast cell stabilizers (cromolyn sodium) Anticholinergics (ipratropium) Various OTC agents and remedies Clinical pearl: best for treating DRAINAGE Oral corticosteroids/antibiotics as a last resort 2

10/14/2014 New developments in OTC medication status The first nasal corticosteroid to go OTC: Triamcinolone acetonide (Nasacort) What to do if your patient’s quality of life is Clinical Pearl : Correct technique for use of nasal still not satisfactory? spray ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ Ketotifen eye drops are now OTC (Zaditor, Alaway)  antihistamine/mast cell stabilizer ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ Montelukast (Singulair) is NOT going OTC any time soon. Allergic Rhinitis/Asthma/Conjunctivitis Testing for specific inhalant allergens Inhaled Allergens Serum specific IgE testing (examples)  Dermatophagoides farinae ; Dermatophagoides pteronyssinus (dust mites) Categories of Management options:  Cat  Cedar/cypress 1. Maximal preventive measures  Oak, birch, sycamore, elm  Rye grass 2. Treatment of symptoms  Ragweed, English plantain 3. Retraining of the immune system  Alternaria  Aspergillus 3

10/14/2014 Testing for Specific Allergens 1. Maximal Preventive Measures Prick skin testing/intradermal testing Personalized counseling avoidance measures: Dust mite cleaning Humidity control Air filtration improvement (HEPA filters) Pollen/mold spore count awareness Mold remediation (indoor and out) Others Photo by: Gundling Which allergen is most associated with Which allergen is most associated with death due to severe asthma ? death due to severe asthma ? A. Alternaria A. Alternaria B. Cat B. Cat C. Dust mites C. Dust mites D. Rye grass D. Rye grass cdc.gov 4

10/14/2014 Allergic Rhinitis/Asthma/Conjunctivitis 3. Retraining of the Immune System Inhaled Allergens Allergen Immunotherapy ‐ subcutaneous “SCIT” Generally works very well Categories of Management options: Very time consuming Requires injections every 1 ‐ 4 weeks 1. Maximal preventive measures Associated risks 2. Treatment of symptoms New kid on the block! 3. Retraining of the immune system Oral or “sublingual” allergen immunotherapy S ub l ingual I mmuno t herapy 2014 – New FDA Approvals Five grass sublingual tablet SLIT ‐ tablets – Oralair by Stallergenes (approved for ages 10 ‐ 65) – Rapidly dissolving tablet held under the tongue until dissolved Timothy grass tablet – Grastek by Merck (approved for ages 5 ‐ 65) – Self ‐ administered, once daily Short ragweed tablet SLIT ‐ drops – Ragwitek by Merck (approved for ages 18 ‐ 65) – Extract of allergen held under the tongue, then swallowed (Existing off ‐ label use of some drops for the past – Self ‐ administered, once daily several years) 5

10/14/2014 Advantages of SLIT Mechanism of Action Can be self ‐ administered at home (for the most part) Probably safer than SCIT Disadvantages of SLIT Limited kinds of antigens (allergens) May not work quite as well as SCIT Long ‐ term benefit of SCIT is better known Public domain: NCI Picture by K Gundling Mechanism of Action Mechanism of Action Changes to both humoral and cellular immunity Gut ‐ associated lymphoid tissue (GALT) Tonsils/lymphoid tissue of the posterior pharynx Antigen uptake by mucosal dendritic cells Peyer’s patches throughout the small intestine Presentation to T cells in the draining lymph nodes Lymphoid organs (mesenteric lymph nodes, Activation of T regulatory cells spleen and liver) Upregulation of IL ‐ 10 Increasing levels of specific IgG4 Gut mucosal immune system TRIES to tolerate Downregulation of mucosal mast cells/effector cells non ‐ pathogens. Blunting of seasonal increases of specific IgE Increased CD8+ T cells 6

10/14/2014 Influenza vaccination Adverse effects/contraindications of SLIT  >/= 5% experience itching/pain of the oropharynx “Doctor, I am allergic to eggs. Can I receive the  Cough flu vaccine?”  Risk of systemic reactions  Not for pts with severe, uncontrolled asthma A. Just give the vaccine  Prescribe epinephrine and train in appropriate use B. Allergy skin test to hen’s egg C. Allergy skin test to the vaccine Approved for use in Europe in 2008 and authorized in 31 countries D. Give a test dose More than 20 million doses have been given to more than 110,000 pts. E. Avoid completely ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ Influenza vaccination “Doctor, I am allergic to eggs. Can I receive the flu vaccine?” A. Just give the vaccine But wait…….. B. Allergy skin test to hen’s egg C. Allergy skin test to the vaccine D. Give a test dose E. Avoid completely 7

10/14/2014 Influenza 294,128 hospitalizations What is the best approach to administration of 23,609 deaths the influenza vaccine in patients who are allergic to hen’s egg? Much of this morbidity and mortality can be prevented with vaccination. Estimates of deaths associated with seasonal influenza—US, 1976 ‐ 2007. MMWR 2010; 59:1057 ‐ 62. Thompson, et al. Influenza associated hospitalizations in the US. JAMA 2004;292:1333 ‐ 40 Ovalbumin content of vaccines (Inactivated, trivalent) Name Manufacturer Content Egg Allergy Afluria CSL Limited <1.0 mcg/0.5mL Prevalence 0.5 ‐ 2% in small children; lower in adults Fluarix GlaxoSmithKline 0.05 Flucelvax Novartis Not in package 5 ‐ 20% of US citizens receive the Vaccines insert influenza vaccination ‐ FluLaval ID Biomedical <0.3 (about 15 ‐ 60 million vaccines Corp annually) Fluvirin Novartis <1.0 Vaccines Photo by Andrei Fluzone Sanofi Pasteur Not in package insert 8

10/14/2014 Vaccination reactions in egg allergic 3,640 patients with reported egg allergy in an patients adjuvanted H1N1 vaccine: 7 published studies – 1.2% had skin reactions – 0.7% had respiratory reactions, including 2 that 1600 patients with egg allergy were given epinephrine (authors concluded these 0 ‐ 6.3% involve reactions confined to the skin reactions were not anaphylaxis) 0 ‐ 4.8% involve mild respiratory or GI symptoms Studies with non egg ‐ allergic controls: No hypotension Similar rates of reactions No need for epinephrine As of 2 years ago… Recommendations for Influenza Vaccination in 185 patients with a history of anaphylaxis or severe reaction to egg ingestion, vaccinated with TIV: the Egg Allergic Patient : – 119 received a divided dose Type of reaction… – 66 received a single dose HIVES ONLY: – No serious reactions ok to administer vaccine in a primary care setting POSSIBLE SYSTEMIC REACTION: refer to A/I office for work ‐ up of the egg allergy Howe LE, et al. Safe administration of seasonal influenza vaccine to children with administration in a setting prepared for egg allergy of all severities. Ann Allergy Asthma Immunol 2011; 106:446 ‐ 7 Webb L, et al. Single ‐ dose influenza vaccination of patients with egg allergy in a anaphylaxis multicenter study. JACI 2011; 128:218 ‐ 9 9

10/14/2014 As of 11 months ago…. . “Flublok” Recombinant hemagglutinin proteins produced in an insect cell line. “ Flucelvax ” Prepared from virus propagated in cell culture These vaccines use no egg protein Fall armyworm Public domain ‐ US govt The CDC’s revised position: The trivalent influenza vaccination is contraindicated in patients with, “History of severe allergic reaction to any component of the vaccine, The main advantage of the RIV is that it can be including egg protein, or after a previous dose of PRODUCED QUICKLY any influenza vaccine.” CDC recommendation this past year: RIV for patients with egg allergy http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6207a1. htm?s_cid=rr6207a1_w#Fig2 10